Dietary l-carnitine regulates liver lipid metabolism via simultaneously activating fatty acid ß-oxidation and suppressing endoplasmic reticulum stress in large yellow croaker fed with high-fat diets.

Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) ß-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial ß-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal ß-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating ß-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA ß-oxidation capability and suppressing the ER stress pathway in fish.

Effects of dietary eucommia ulmoides leaf extract on growth performance, expression of feeding-related genes, activities of digestive enzymes, antioxidant capacity, immunity and cytokines expression of large yellow croaker (Larimichthys crocea) larvae.

A 30-d feeding trial was conducted to investigate effects of dietary eucommia ulmoides leaf extract (ELE) on growth performance, activities of digestive enzymes, antioxidant capacity, immunity, expression of inflammatory factors and feeding-related genes of large yellow croaker larvae. Five micro-diets were formulated with supplementation of 0 g kg-1 (the control), 5 g kg-1 (0·5 %), 10 g kg-1 (1·0 %) and 20 g kg-1 (2·0 %) of ELE, respectively. Results showed that the best growth performance was found in larvae fed the diet with 1·0 % ELE. Furthermore, ELE supplementation significantly increased the npy expression at 1·0 % dosage, while increased ghrelin in larvae at 0·5 % dosages. The activity of leucine aminopeptidase in larvae fed the diet with 1·0 % ELE was significantly higher than the control, while alkaline phosphatase was significantly upregulated in larvae fed the diet with 2·0 % ELE. A clear increase in total antioxidant capacity in larvae fed the diet with 1·0 % ELE was observed, whereas catalase activity was significantly higher in 1·0 % and 2·0 % ELE supplementation compared with the control. Larvae fed the diet with 1·0 % ELE had a significantly higher activities of lysozyme, total nitric oxide synthase and nitric oxide content than the control. Moreover, transcriptional levels of cox-2, il-1ß and il-6 were remarkably downregulated by the supplementation of 0·5-1·0 % ELE. This study demonstrated that the supplementation of 1·0 % ELE in diet could increase the growth performance of large yellow croaker larvae probably by promoting expression of feeding-related genes, enhancing antioxidant capacity and immunity and inhibiting expression of inflammatory factors.

Bacteria-Mediated Tumor Therapy via Photothermally-Programmed Cytolysin A Expression.

By leveraging the ability of bacteria to express therapeutic protein cytolysin A (ClyA) through plasmid transformation, a thermally-activated biohybrid (TAB@Au) is constructed by biomineralizing gold nanoparticles (AuNPs) on the E. coli surface. Due to the feature of anaerobic bacteria homing to tumor microenvironments, the bacteria-based antitumor vehicles can be efficaciously accumulated at tumor sites. Under NIR laser irradiation, the biomineralized AuNPs harvest transdermal photons and convert them into local heat for photothermal therapy. After that, the produced heat elicits the expression of ClyA for killing tumor cells. In vitro and in vivo experiments verify the conception that the current therapeutic modality greatly inhibits the proliferation of tumor cells. In terms of the spatial specificity and non-invasiveness of NIR laser, the bacteria-based phototherapy represents an appealing way for tumor therapy.

Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism.

Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when activated in response to liver injury are characterized with many changes, with HSC contraction being the most common cause of portal hypertension. Previous studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic natural product by inducing HSC apoptosis, whereas the role of DHA in regulating HSC contraction and the mechanisms involved remain a riddle. Recent studies have emphasized on the importance of farnesoid X receptor (FXR) and sphingosine-1-phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed that DHA strongly induced the mRNA and protein expression of FXR in LX-2 cells in a dose- and time-dependent manner and inhibited HSC activation, implying a conceivable impact of DHA on HSC contraction. The gel contraction assays and fluorescence staining of actin cytoskeleton verified that DHA dose-dependently limited contraction of collagen lattices and reorganization of actin stress fibers in LX-2 cells. DHA also decreased the phosphorylation of myosin light chain that is responsible for the contractile force of HSCs. Furthermore, gain- or loss-of-function analyses exhibited a FXR- and S1PR2-dependent mechanism of inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by modulating FXR activation. Subsequent work revealed that inhibition of both Ca(2+) -dependent and Ca(2+) -sensitization signaling transductions contributed to DHA-induced HSC relaxation. In summary, these findings suggest that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. © 2016 IUBMB Life 68(5):376-387, 2016.